BMPR2 pathway Expression in different types of pulmonary arterial hypertensio

Recruitment & Eligibility

Status: Complete

Sex: All

Target Recruitment: 220

Inclusion Criteria

All participants (PAH patients, healthy plant carriers, healthy controls):
- Age of majority
- Capacity to give consent
- Written informed consent

PAH patients
- Mean pulmonary arterial pressure (mPAP) =25 mmHg, pulmonary vascular resistance =3 WU, pulmonary arterial occlusion pressure (PAWP) =15 mmHg.

HPAH patients
- Molecularly detected (probable) pathogenic variant in a PAH gene.

IPAH patients
- Guideline diagnosis of IPAH

SSc-APAH patients
- Rheumatologically confirmed systemic sclerosis according to the American College of Rheumatology / European League against Rheumatism criteria

Other APAH patients
- Guideline diagnosis of APAH

PAH patients with comorbidities.
- Age =65 years
- Either at least three of these cardiac/metabolic comorbidities: systemic arterial hypertension, coronary artery disease, diabetes mellitus, BMI =30 kg/m2, left atrial enlargement, atrial fibrillation;
- And/Or: pulmonary comorbidities such as chronic obstructive pulmonary disease (COPD) or interstitial lung disease with (near) normal lung function parameters: forced expiratory volume in one second (FEV1) =60%, forced vital capacity =70%

CTEPH patients
- Guideline diagnosis of CTEPH.

Healthy variant carriers
- Presence of hereditary PAH diagnosis (HPAH) in a close relative.
- Proven genetic variant predisposing to PAH
- No evidence of pulmonary hypertension in screening examination including echocardiography

Healthy controls
- Age- and sex-matched group in relation to the IPAH patients
- Blood collection after informed consent or
- Participants of the Lung Biobank Heidelberg of the Translational Research Section, Thoraxklinik Heidelberg, and Platform Biobanking & Data Management of the German Center for Lung Research (DZL)

Exclusion Criteria

All (PAH patients, healthy variant carriers, healthy controls):
- Pregnancy, lactation
- Acute infection

PAH patients with comorbidities.
- Significant lung disease: COPD with FEV1 <60% pred, IPF with FVC <70% pred, CT =20% fibrosis.

Healthy controls
- Significant cardiac or pulmonary disease
- Acute malignant tumor disease
- Comorbidities that may be triggered by the BMPR2 pathway: Brachydactyly, short stature, hemochromatosis (BMPR1B, BMP9); microphthalamia (BMP4); Myhre syndrome (SMAD4); craniosynastosis (SMAD6); proximal symphalangism/multiple synostoses syndrome (Noggin); sclerosteosis (Sclerostin), Loeys-Dietz syndrome (SMAD3).

Study & Design

Study Type: observational

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
BMPR2 mRNA expression in HPAH patients (positive control) and healthy study participants (negative control) compared with IPAH, CTEPH patients, patients with systemic sclerosis-associated PAH (SSc-APAH), healthy BMPR2 plant carriers, and PAH patients with comorbidities.

Secondary Outcome Measures